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Alexander H, Falk R, Utz S, Felix D, Aladdin AD, Hermann K, Laura S, Johanna B, Michael A. Comparison of different liver fibrosis scores following sleeve gastrectomy. Langenbecks Arch Surg 2025; 410:29. [PMID: 39775103 DOI: 10.1007/s00423-024-03569-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 12/04/2024] [Indexed: 01/11/2025]
Abstract
PURPOSE The prevalence of obesity, along with that of its associated health conditions, including cardiovascular diseases, diabetes mellitus, and liver diseases, such as non-alcoholic fatty liver disease (NAFLD), is increasing annually. Bariatric surgery is indicated for the treatment of obesity if conservative treatment fails. While various liver fibrosis scores have been proposed for assessing liver function, they are typically used prior to bariatric surgery. This study aimed to determine whether fibrosis scores calculated from non-invasive parameters are effective in monitoring liver function after bariatric surgery. METHODS This study analyzed data from 151 patients who underwent sleeve gastrectomy (SG) and were followed up at 3, 6, 9, 12, 24, and 36 months postoperatively. From the routinely collected parameters, liver fibrosis scores (APRI, Fib-4, BARD, Forns index [FORNS], Lok score [LOK], and NAFLD scores) were calculated retrospectively and compared to diabetes status % excess weight loss (%EWL) and % total weight loss (%TWL) over a 3-year follow-up period. RESULTS After SG, APRI, FORNS, and NAFLD scores showed significant improvements, whereas Fib-4, BARD, and LOK scores did not improve. Similarly, body mass index, %EWL, %TWL, and diabetes status also improved significantly. Throughout the 3-year follow-up period, only the APRI and NAFLD scores showed significant improvement. CONCLUSION Only APRI and NAFLD scores changed significantly after SG. Thus, these two scores may be used to reflect and monitor liver function in patients who have undergone SG.
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Affiliation(s)
- Heilberger Alexander
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany.
| | - Rauchfuss Falk
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Settmacher Utz
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Dondorf Felix
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Ali Deeb Aladdin
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Kissler Hermann
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Schwenk Laura
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Bruns Johanna
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Ardelt Michael
- Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Am Klinikum 1, 07747, Jena, Germany
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Terracciani F, Falcomatà A, Gallo P, Picardi A, Vespasiani-Gentilucci U. Prognostication in NAFLD: physiological bases, clinical indicators, and newer biomarkers. J Physiol Biochem 2023; 79:851-868. [PMID: 36472795 DOI: 10.1007/s13105-022-00934-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 11/23/2022] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is becoming an epidemic in Western countries. Notably, while the majority of NAFLD patients will not evolve until advanced liver disease, a minority of them will progress towards liver-related events. Therefore, risk stratification and prognostication are emerging as fundamental in order to optimize human and economic resources for the care of these patients.Liver fibrosis has been clearly recognized as the main predictor of poor hepatic and extrahepatic outcomes. However, a prediction based only on the stage of fibrosis is near-sighted and static, as it does not capture the propensity of disease to further progress, the speed of progression and their changes over time. These determinants, which result from the interaction between genetic predisposition and acquired risk factors (obesity, diabetes, etc.), express themselves in disease activity, and can be synthesized by biomarkers of hepatic inflammation and fibrogenesis.In this review, we present the currently available clinical tools for risk stratification and prognostication in NAFLD specifically with respect to the risk of progression towards hard hepatic outcomes, i.e., liver-related events and death. We also discuss about the genetic and acquired drivers of disease progression, together with the physiopathological bases of their come into action. Finally, we introduce the most promising biomarkers in the direction of repeatedly assessing disease activity over time, mainly in response to future therapeutic interventions.
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Affiliation(s)
- Francesca Terracciani
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Andrea Falcomatà
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Paolo Gallo
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy.
| | - Antonio Picardi
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
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Nguyen VH, Le I, Ha A, Le RH, Rouillard NA, Fong A, Gudapati S, Park JE, Maeda M, Barnett S, Cheung R, Nguyen MH. Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study. Clin Mol Hepatol 2023; 29:1002-1012. [PMID: 37691484 PMCID: PMC10577349 DOI: 10.3350/cmh.2023.0205] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/05/2023] [Accepted: 09/07/2023] [Indexed: 09/12/2023] Open
Abstract
BACKGROUND/AIMS Understanding of nonalcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients. METHODS Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995-2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related). RESULTS The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5-3.5% and 4.3-7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022). CONCLUSION Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.
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Affiliation(s)
- Vy H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Harvard Medical School, Boston, MA, USA
| | - Isaac Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Emory University, Atlanta, GA, USA
| | - Audrey Ha
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Richard Hieu Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- William Carey University College of Osteopathic Medicine, Hattiesburg, MS, USA
| | - Nicholas Ajit Rouillard
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Ashley Fong
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Surya Gudapati
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Washington University, St Louis, MO, USA
| | - Jung Eun Park
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Mayumi Maeda
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Scott Barnett
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Palo Alto Veterans Affairs Medical Center, Palo Alto, CA, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
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Liao C, Liang X, Zhang X, Li Y. The effects of GLP-1 receptor agonists on visceral fat and liver ectopic fat in an adult population with or without diabetes and nonalcoholic fatty liver disease: A systematic review and meta-analysis. PLoS One 2023; 18:e0289616. [PMID: 37616255 PMCID: PMC10449217 DOI: 10.1371/journal.pone.0289616] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 07/22/2023] [Indexed: 08/26/2023] Open
Abstract
AIM To uncover the effect of GLP-1 receptor agonists (GLP-1 RAs) on the visceral- and hepatic fat content of adults. METHODS PubMed, EMBASE, Cochrane Library, and Web of Science were searched from inception until November 2022. Randomized controlled trials (RCTs) of GLP-1Ras was extracted, including reports of effects on visceral adipose tissue and hepatic fat content in individuals with type 2 diabetes, non-type 2 diabetes, NAFLD (non-alcoholic fatty liver disease), and non-NAFLD. Meta-analyses used random-effects models. RESULTS 1736 individuals in the 30 qualified RCTs were included, comprising 1363 people with type 2 diabetes and 318 with NFLD. GLP-1 RAs reduced visceral adipose tissue (standard mean difference [SMD] = -0.59, 95% CI [-0.83, -0.36], P<0.00001) and hepatic fat content (weighted mean difference [WMD] = -3.09, 95% CI [-4.16, -2.02], P<0.00001) compared to other control treatment. Subgroup analysis showed that GLP-1Ras dramatically decreased visceral fat in patients with type 2 diabetes (SMD = -0.49, 95% CI [-0.69, -0.29] P<0.00001), NAFLD (SMD = -0.99, 95% CI [-1.64, -0.34] P = 0.003), non-type 2 diabetes (SMD = -1.38, 95% CI [-2.44, -0.32] P = 0.01), and non-NAFLD (SMD = -0.53, 95% CI [-0.78, -0.28] P<0.0001). GLP-1Ras reduced the liver fat level of type 2 diabetes (WMD = -3.15, 95% CI [-4.14, -2.15] P<0.00001), NAFLD (WMD = -3.83, 95% CI [-6.30, -1.37] P = 0.002), and type 2 diabetes with NAFLD (WMD = -4.27, 95% CI [-6.80, -1.74] P = 0.0009), while showed no impact on the hepatic fat content in non-Type 2 diabetes (WMD = -12.48, 95% CI [-45.19, 20.24] P = 0.45). CONCLUSIONS LP-1 RAs significantly reduce visceral- and liver fat content in adults.
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Affiliation(s)
- Chao Liao
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Xinyin Liang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Xiao Zhang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Yao Li
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
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Huang Q, Yu H, Zhong X, Tian Y, Cui Z, Quan Z. Association between hypertension and nonalcoholic fatty liver disease: a cross-sectional and meta-analysis study. J Hum Hypertens 2023; 37:313-320. [PMID: 35411023 DOI: 10.1038/s41371-022-00686-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 03/11/2022] [Accepted: 03/30/2022] [Indexed: 11/08/2022]
Abstract
The association between hypertension and nonalcoholic fatty liver disease (NAFLD) is not completely understood. This study aimed to investigate the association between hypertension and hepatic ultrasound examination-diagnosed positive NAFLD in healthy people; to conduct a comprehensive meta-analysis combining the results of previous studies; to explore whether hypertension was a risk factor for NAFLD. This study included 2049 adults (male: 870 and female: 1179), aged ≥20 years, whose anthropometric parameters were measured to analyze the risk of hypertension on NAFLD. We also collected data from 11 cross-sectional studies relevant to this topic using PubMed, Embase, Web of Science, CNKI, Wanfang, and CQVIP from beginning till 31 August 2020 and combined it with our data for a meta-analysis to explore whether hypertension was a risk factor for NAFLD. After adjusting for confounding factors, the odds of NAFLD in hypertensive subjects was 1.473 (95%CI: 1.119-1.938). After combining with 10 selected studies, 42711 participants were enrolled in meta-analysis. Hypertension was a risk factor for NAFLD (Z = 13.46, P < 0.001); the odds of NAFLD in hypertensive subjects was 1.43 (95%CI: 1.36-1.51). The results were consistent with the results of the meta-analysis. Further studies are required to confirm these results.
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Affiliation(s)
- Qingzhi Huang
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Hana Yu
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Xin Zhong
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Ying Tian
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China
| | - Zhenhua Cui
- Department of Nephrology, Yanbian University Hospital, 119 Juzi Street, Yanji, 133000, Jilin, China
| | - Zhenyu Quan
- Department of Preventive Medicine, Medical College, Yanbian University, 977 Gongyuan Street, Yanji, 133000, Jilin, China.
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6
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Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of Liver Disease: 2023 Update. J Hepatol 2023:S0168-8278(23)00194-0. [PMID: 36990226 DOI: 10.1016/j.jhep.2023.03.017] [Citation(s) in RCA: 624] [Impact Index Per Article: 312.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/06/2023] [Accepted: 03/09/2023] [Indexed: 03/31/2023]
Abstract
Liver disease accounts for 2 million deaths and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately 2/3 of all liver related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and nonalcoholic fatty liver disease (NAFLD). Hepatotropic viruses are the etiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, NAFLD, viral hepatitis, and HCC. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.
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Affiliation(s)
- Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, India
| | - Sumeet K Asrani
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX, United States.
| | - Juan Pablo Arab
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Yvonne Ayerki Nartey
- Department of Internal Medicine, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Elisa Pose
- Liver Unit, Hospital Clinic of Barcelona. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, MN, United States
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Lin H, Yip TCF, Zhang X, Li G, Tse YK, Hui VWK, Liang LY, Lai JCT, Chan SL, Chan HLY, Wong GLH, Wong VWS. Age and the relative importance of liver-related deaths in nonalcoholic fatty liver disease. Hepatology 2023; 77:573-584. [PMID: 35790018 DOI: 10.1002/hep.32633] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 06/22/2022] [Accepted: 06/22/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND AND AIMS It is unclear if the leading causes of death in patients with NAFLD differ by age. We aimed to investigate if the relative importance of liver-related deaths is lower and overshadowed by cardiovascular and cancer-related deaths in the elderly population. APPROACH AND RESULTS We conducted a territory-wide retrospective cohort study of adult patients with NAFLD between 2000 and 2021 in Hong Kong. The outcomes of interest were all-cause and cause-specific mortality. Age groups at death were studied at 10-year intervals. During 662,471 person-years of follow-up of 30,943 patients with NAFLD, there were 2097 deaths. The top three causes of death were pneumonia, extrahepatic cancer, and cardiovascular diseases. Liver disease was the sixth leading cause of death in patients aged 70-79 and 80-89 years, accounting for 5.1% and 5.9% of deaths, respectively, but only accounted for 3% or fewer of the deaths in the other age groups. Nonetheless, liver disease was the leading cause of death in patients with NAFLD-related cirrhosis, accounting for 36.8% of all deaths. The incidence of liver-related death was higher in men younger than age 70 but higher in women afterwards. The incidence of liver-related death in women increased from 0.62 to 7.14 per 10,000 person-years from age 60-69 to 70-79 years. CONCLUSION The relative importance of liver-related death increases with age in patients with NAFLD, especially among women. In patients with cirrhosis, liver disease is the leading cause of death.
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Affiliation(s)
- Huapeng Lin
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Xinrong Zhang
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Guanlin Li
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Yee-Kit Tse
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Vicki Wing-Ki Hui
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Lilian Yan Liang
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Jimmy Che-To Lai
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Stephen Lam Chan
- Department of Clinical Oncology , Sir YK Pao Centre for Cancer , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Translational Oncology , The Chinese University of Hong Kong , Hong Kong , China
| | - Henry Lik-Yuen Chan
- Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,Union Hospital , Hong Kong , China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics , The Chinese University of Hong Kong , Hong Kong , China.,Medical Data Analytics Centre , The Chinese University of Hong Kong , Hong Kong , China.,State Key Laboratory of Digestive Disease , The Chinese University of Hong Kong , Hong Kong , China
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Vitale A, Svegliati-Baroni G, Ortolani A, Cucco M, Dalla Riva GV, Giannini EG, Piscaglia F, Rapaccini G, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Marra F, Mega A, Morisco F, Gasbarrini A, Foschi FG, Missale G, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Oliveri F, Pelizzaro F, Ramirez Morales R, Cillo U, Trevisani F, Miele L, Marchesini G, Farinati F. Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002-2033: the ITA.LI.CA database. Gut 2023; 72:141-152. [PMID: 34933916 DOI: 10.1136/gutjnl-2021-324915] [Citation(s) in RCA: 86] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort. METHODS We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC. RESULTS MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006). CONCLUSIONS The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Gianluca Svegliati-Baroni
- Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Obesity Center, Polytechnic University of Marche, Ancona, Italy
| | - Alessio Ortolani
- Department of Gastroenterology, Azienda Ospedaliera Marche Nord Pesaro, Pesaro, Italy
| | - Monica Cucco
- Liver Disease and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy
| | - Giulio V Dalla Riva
- School of Mathematics and Statistics University of Canterbury, Statistics University of Canterbury, Canterbury, New Zealand
| | - Edoardo G Giannini
- Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genoa, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianludovico Rapaccini
- Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | | | | | - Marco Zoli
- Department of Medical and Surgical Sciences, Internal Medicine-Zoli Unit, Alma Mater Studiorum - Università di Bologna, Padova, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Puglia, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy
| | - Andrea Mega
- Gastroenterology Unit, Ospedale Generale Regionale di Bolzano, Bolzano, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Portici, Italy
| | - Antonio Gasbarrini
- Internal Medicine, Gastroenterology, and Liver Unit, University Hospital Agostino Gemelli, Roma, Lazio, Italy
| | | | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Emilia-Romagna, Italy
| | - Alberto Masotto
- Gastroenterology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Veneto, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, Federico II University Hospital, Napoli, Italy
| | - Giovanni Raimondo
- Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy
| | - Francesco Azzaroli
- Division of Gastroenterology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Clinical and Experimental Medicine, Universita degli Studi di Sassari, Sassari, Italy
| | - Filippo Oliveri
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Pisa, Italy
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Rafael Ramirez Morales
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Franco Trevisani
- Division of Medical Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luca Miele
- Internal Medicine and Gastroenterology, Fondazione Policlinico Gemelli, Rome, Italy
- Internal Medicine, Universita Cattolica del Sacro Cuore, Roma, Italy
| | - Giulio Marchesini
- Department of Medical & Surgical Sciences, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
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9
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Wang D, Xu Y, Zhu Z, Li Y, Li X, Li Y, Shen H, Wu W, Liu Y, Han C. Changes in the global, regional, and national burdens of NAFLD from 1990 to 2019: A systematic analysis of the global burden of disease study 2019. Front Nutr 2022; 9:1047129. [PMID: 36618688 PMCID: PMC9811393 DOI: 10.3389/fnut.2022.1047129] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 11/30/2022] [Indexed: 12/24/2022] Open
Abstract
Background Understanding the burdens and trends of non-alcoholic fatty liver disease (NAFLD) is necessary for developing effective intervention strategies. In this study, Global Burden of Disease (GBD) 2019 study data were extracted and analyzed to elucidate trends of NAFLD. Methods The prevalence, incidence, disability-adjusted life year (DALY), and death rates of NAFLD in geographic populations worldwide from 1990 to 2019 were extracted from the GBD 2019 study data. The global temporal trend of NAFLD from 1990 to 2019 was evaluated using estimated annual percentage changes (EAPCs) and age-standardized rates. Results Globally, between 1999 and 2019, the age-standardized prevalence rate of NAFLD increased, with EAPCs of 0.77 [95% CI (0.69, 0.85)], whereas the DALY and Death rates decreased, with EAPCs of -0.82 [95% CI (-0.92, -0.71)], and -0.67 [95% CI (-0.76, -0.58)], respectively. Geographically, the age-standardized prevalence rate showed the most serious upward trend in high-income North America with an EAPC of 0.98 [95% CI (0.95, 1.02)], and the age-standardized incidence rate showed an upward trend in Central Asia with an EAPC of 3.17 [95% CI (2.2, 2.49)]. The most significant upward trend of DALY and death rates appeared in Eastern Europe, with EAPCs of 4.06 [95% CI (3.31, 4.82)], and 3.36 [95% CI (2.77, 3.96)], respectively. At the country level, the age-standardized rates showed an upward trend in Armenia, Belarus, and Republic of Korea. Regarding age groups, the percentage change of prevalence was the highest in the 40 to 44 group [0.29 (0.26, 0.34)] from 1990 to 2019; the percentage change of incidence was the highest in the 85 to 89 group [0.46 (0.12, 0.71)] from 1990 to 2019; the percentage change of DALY was the highest in the 80 to 84 group [0.25 (0.11, 0.39)] from 1990 to 2019; and the percentage change of death rate was the highest in the 15 to 19 group [0.36 (0.17, 0.60)] from 1990 to 2019. The percentage change of prevalence of liver cancer due to NASH was the highest in the group of 85 to 89, whereas those of incidence, DALY, and death were the highest in the group above 95 from 1990 to 2019. Regarding the sociodemographic index (SDI), the highest age-standardized prevalence, incidence, and Death rates of NAFLD occurred in middle-SDI countries, and the highest DALY rates of NAFLD occurred in low-SDI countries. Conclusion Global NAFLD burdens have increased since 1990. Our findings provide a reference for policymakers to reduce the burden of NAFLD, especially in middle and low-SDI countries.
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Affiliation(s)
- Dan Wang
- Department of Clinical Nutrition and Metabolism, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Yanbing Xu
- Department of Clinical Nutrition and Metabolism, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Zizhao Zhu
- Department of General Surgery, The Sixth People’s Hospital of Shenyang, Shenyang, China
| | - Yanliang Li
- Departments of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, United States
| | - Xiaowen Li
- Department of Clinical Nutrition and Metabolism, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Yike Li
- Department of Clinical Nutrition and Metabolism, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Hui Shen
- Department of Clinical Nutrition and Metabolism, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Wei Wu
- Department of General Surgery, The Sixth People’s Hospital of Shenyang, Shenyang, China
| | - Yazhuo Liu
- Department of Clinical Nutrition and Metabolism, Affiliated Zhongshan Hospital of Dalian University, Dalian, China,*Correspondence: Yazhuo Liu,
| | - Cheng Han
- Department of Clinical Nutrition and Metabolism, Affiliated Zhongshan Hospital of Dalian University, Dalian, China,Cheng Han,
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10
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Huang C, Wei X, Luo Q, Xia Y, Pan T, He J, Jahangir A, Jia L, Liu W, Zou Y, Li L, Guo H, Geng Y, Chen Z. Loss of TRIM67 Attenuates the Progress of Obesity-Induced Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2022; 23:ijms23137475. [PMID: 35806477 PMCID: PMC9267895 DOI: 10.3390/ijms23137475] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/01/2022] [Accepted: 07/02/2022] [Indexed: 02/01/2023] Open
Abstract
Obesity is considered as a major cause for the development and progress of non-alcoholic fatty liver disease (NAFLD), which is one of the most prevalent chronic liver diseases worldwide. However, molecular mechanisms that implicate in obesity-driven pathophysiology of NAFLD are not well defined. Here, we report a tripartite motif (TRIM) protein family member—TRIM67—that is hardly expressed in liver but is inducible on obese conditions. Enhanced expression of TRIM67 activates hepatic inflammation to disturb lipid metabolic homeostasis and promote the progress of NAFLD induced by obesity, while the deficiency in TRIM67 is protective against these pathophysiological processes. Finally, we show that the important transcription coactivator PGC-1α implicates in the response of hepatic TRIM67 to obesity.
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Affiliation(s)
- Chao Huang
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
- Correspondence: (C.H.); (Z.C.)
| | - Xiaoli Wei
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Qihui Luo
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Yu Xia
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Ting Pan
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Junbo He
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Asad Jahangir
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Lanlan Jia
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Wentao Liu
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Yuanfeng Zou
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Lixia Li
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Hongrui Guo
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Yi Geng
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
| | - Zhengli Chen
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (X.W.); (Q.L.); (Y.X.); (T.P.); (J.H.); (A.J.); (L.J.); (W.L.)
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (L.L.); (H.G.); (Y.G.)
- Correspondence: (C.H.); (Z.C.)
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Li X, Lang X, Peng S, Ding L, Li S, Li Y, Yin L, Liu X. Calf Circumference and All-Cause Mortality: A Systematic Review and Meta-Analysis Based on Trend Estimation Approaches. J Nutr Health Aging 2022; 26:826-838. [PMID: 36156674 DOI: 10.1007/s12603-022-1838-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES To perform a systematic review and meta-analysis and quantify the associations of total mortality with calf circumference (CC) in adults 18 years and older via combining various analyses based on empirical dichotomic CC, continuous CC, and dose-response CC. METHODS We conducted a systematic search of relevant studies in PubMed, EMBASE, Cochrane Library, and Web of Science published through April 12, 2022. This systematic review includes longitudinal observational studies reporting the relationships of total mortality with CC. We calculated the pooled relative risk (RR) and 95% confidence interval (CI) of total mortality with CC per 1 cm for each study and combined the values using standard meta-analysis approaches. Newcastle-Ottawa scale (NOS), Grading of Recommendations, Assessment, Development and Evaluations approach (GRADE), and the Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN) were assessed for meta-analyses. RESULTS Our analysis included a total of 37 cohort studies involving 62,736 participants, across which moderate heterogeneity was observed (I2=75.7%, P<0.001), but no publication bias was found. Study quality scores ranged from 6 to 9 (mean 7.7), with only three studies awarded a score of 6 (fair quality). We observed an inverse trend between total death risk and CC per 1 cm increase (RR, 0.95, 95% CI, 0.94-0.96; P<0.001; GRADE quality=high). Only a very slight difference was found among residents of nursing homes (6.9% mortality risk reduction per one cm CC increase), community-dwellers (5.4%), and those living in hospitals (4.8%), respectively (P for meta-regression=0.617). Low credible subgroup difference was found based on the ICEMAN tool. CONCLUSIONS Calf circumference is a valid anthropometric measure for mortality risk prediction in a community, nursing home, or hospital.
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Affiliation(s)
- X Li
- Lu Yin, Medical Research and Biometrics Center, National Center for Cardiovascular Diseases, Beijing 102300, China. E-mail: ; Xiaomei Liu, Department of Emergency, Zhongshan Hospital of Xiamen University, Xiamen, China. Tel:
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12
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Premkumar M, Anand AC. Tobacco, Cigarettes, and the Liver: The Smoking Gun. J Clin Exp Hepatol 2021; 11:700-712. [PMID: 34866849 PMCID: PMC8617531 DOI: 10.1016/j.jceh.2021.07.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 07/29/2021] [Indexed: 12/12/2022] Open
Abstract
The association between alcohol and liver disease, including alcoholic hepatitis, cirrhosis, acute-on-chronic liver failure, and hepatocellular carcinoma, has been well described, but the same cannot be said for the association between smoking, water pipe or tobacco chewing. A review of cumulative evidence suggests that smoking is independently a risk factor for liver fibrosis and contributes to carcinogenesis in HCC. Smoking-related fibrosis has been reported in patients with nonalcoholic fatty liver disease, primary biliary cholangitis, alcoholic liver disease and chronic viral hepatitis. Heavy smoking leads to systemic inflammation, oxidative stress, insulin resistance, and results in tissue hypoxia, as well as free radical damage. Other than damaging the liver, patients also suffer from the systemic effects of the 4000 chemicals associated with tobacco, which include nitrosamines, aromatic hydrocarbons, nicotine, nornicotine, and other alkaloids. These include respiratory ailments, cancer of the lungs, oral cavity, esophagus, pancreas and colon, atherosclerotic vascular disease, and stroke.
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Key Words
- ALP, alkaline phosphatase
- BMI, body mass index
- CLD, chronic liver disease
- GGT, gamma-glutamyl transpeptidase
- HBV, hepatitis B virus
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- HR, hazard ratio
- MetS, metabolic syndrome
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- OR, odds ratio
- RR, relative risk
- ST, smokeless tobacco
- WHO, World Health Organization
- cirrhosis
- hepatocellular carcinoma
- inflammation
- smoking
- tobacco
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Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Anil C Anand
- Department of Hepatology, Kalinga Institute of Medical Sciences, Bhubaneshwar, Odisha, India
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13
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Comparison of Liver Recovery After Sleeve Gastrectomy and Roux-en-Y-Gastric Bypass. Obes Surg 2021; 31:3218-3226. [PMID: 33813683 PMCID: PMC8175244 DOI: 10.1007/s11695-021-05390-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 03/21/2021] [Accepted: 03/25/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a common condition in patients with obesity. Bariatric surgery has often been proposed as a viable treatment option, but the ideal surgical procedure remains unclear. Inconsistently, reports on postoperative deterioration of liver function put further doubt on which technique to apply. Aim of this study was to assess the impact of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on the postoperative recovery of liver function. METHODS A total of 175 patients with obesity that underwent bariatric surgery in our institution were included in this prospective cohort study. BMI, laboratory values, and liver function capacity (using LiMAx) were assessed preoperatively and at 6 and 12 months postoperatively. Generalized linear model (GLM) was performed to determine variables influencing liver function capacity after the operation. RESULTS Prior to operations, 64% of patients presented with a diminished liver function capacity, as measured by LiMAx test. Liver function capacity significantly recovered after 12 months in the SG group (300 μg/kg/h preop vs. 367 μg/kg/h postop) but not in the RYGB group (306 μg/kg/h preop vs. 349 μg/kg/h). Preoperative factors impeding liver function recovery included type 2 diabetes mellitus (T2DM), weight, male sex, AST/thrombocyte ratio (APRI), and gamma-glutamyltransferase (GGT). CONCLUSION Bariatric surgery, especially sleeve gastrectomy, leads to an improvement of liver function. However, in some patients with T2DM, higher preoperative weight and male sex postoperative deterioration of liver function capacity may occur.
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14
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Zaki M, Amin D, Mohamed R. Body composition, phenotype and central obesity indices in Egyptian women with non-alcoholic fatty liver disease. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2020; 18:385-390. [PMID: 34187121 DOI: 10.1515/jcim-2020-0073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 06/12/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The aim of this study is to investigate body composition and phenotype of Egyptian women with non-alcoholic fatty liver disease (NAFLD) and compare with those without and determine the optimal cut-off values of central obesity indices for predicting NAFLD. METHODS The study included 100 women with NAFLD and 100 age and sex matched healthy controls without NAFLD. All women were subjected to ultrasonography examination. Anthropometric measurements included weight, height, waist circumference (WC), hip circumference (HC) and skinfolds thickness were assessed for all participants. Body fat % was evaluated by Tanita body composition analyzer. Body mass index (BMI), WC / height ratio (WHtR), WC / HC ratio (WHR) and visceral adiposity index (VAI) were calculated. Receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values. RESULTS Data showed significant higher levels of WHtR, WHR, BMI, sum of skinfolds, body fat %, serum fasting blood lipids and glucose in NAFLD women compared to group of patients without NAFLD. The area under curve (AUC) was 0.920 for VIA, 0.883 for WHtR and 0.647 for WHR. The optimal cutoff value of VAI was 3.66, of WHtR was 0.66 and WHR was 0.84. All values showed high sensitivity and specificity values. CONCLUSION NAFLD women were obese, had excess subcutaneous fat and body fat ratio. Central obesity indices are closely associated with the presence of NAFLD in Egyptian women and might be responsible for its development. Visceral adiposity index had superior diagnostic performance.
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Affiliation(s)
- Moushira Zaki
- Biological Anthropology Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Darine Amin
- Biological Anthropology Department, Medical Research Division, National Research Centre, Cairo, Egypt
| | - Ramy Mohamed
- Biological Anthropology Department, Medical Research Division, National Research Centre, Cairo, Egypt
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Berardo C, Di Pasqua LG, Cagna M, Richelmi P, Vairetti M, Ferrigno A. Nonalcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: Current Issues and Future Perspectives in Preclinical and Clinical Research. Int J Mol Sci 2020; 21:ijms21249646. [PMID: 33348908 PMCID: PMC7766139 DOI: 10.3390/ijms21249646] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 12/15/2020] [Accepted: 12/16/2020] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a continuum of liver abnormalities often starting as simple steatosis and to potentially progress into nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Because of its increasing prevalence, NAFLD is becoming a major public health concern, in parallel with a worldwide increase in the recurrence rate of diabetes and metabolic syndrome. It has been estimated that NASH cirrhosis may surpass viral hepatitis C and become the leading indication for liver transplantation in the next decades. The broadening of the knowledge about NASH pathogenesis and progression is of pivotal importance for the discovery of new targeted and more effective therapies; aim of this review is to offer a comprehensive and updated overview on NAFLD and NASH pathogenesis, the most recommended treatments, drugs under development and new drug targets. The most relevant in vitro and in vivo models of NAFLD and NASH will be also reviewed, as well as the main molecular pathways involved in NAFLD and NASH development.
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Affiliation(s)
| | | | | | | | | | - Andrea Ferrigno
- Correspondence: (L.G.D.P.); (A.F.); Tel.: +39-0382-986-451 (L.G.D.P.)
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Jarvis H, Craig D, Barker R, Spiers G, Stow D, Anstee QM, Hanratty B. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies. PLoS Med 2020; 17:e1003100. [PMID: 32353039 PMCID: PMC7192386 DOI: 10.1371/journal.pmed.1003100] [Citation(s) in RCA: 258] [Impact Index Per Article: 51.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 04/06/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. METHODS AND FINDINGS We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. CONCLUSIONS In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. TRIAL REGISTRATION PROSPERO CRD42018115459.
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Affiliation(s)
- Helen Jarvis
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
- * E-mail:
| | - Dawn Craig
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Robert Barker
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Gemma Spiers
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Daniel Stow
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Quentin M. Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
- NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
| | - Barbara Hanratty
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
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Huang Y, Joseph J, de Boer WB, Cheng W, Adams LA, MacQuillan G, Garas G, Raftopoulos S, Jeffrey GP. Long-term Liver-related Outcomes of Patients With Chronic Liver Diseases in Australia. Clin Gastroenterol Hepatol 2020; 18:496-504.e3. [PMID: 31319186 DOI: 10.1016/j.cgh.2019.07.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 07/04/2019] [Accepted: 07/09/2019] [Indexed: 01/04/2023]
Abstract
BACKGROUND & AIMS Chronic liver disease is a major health burden that produces significant liver-related morbidity and mortality. We aimed to evaluate liver-related outcomes of patients with different causes of chronic liver disease in Australia. METHODS We collected data from 10,933 patients with chronic liver disease assessed by Hepascore (a serum fibrosis model) in Western Australia from 2004 through 2015. We obtained records of liver-related death, transplantation, decompensation, and hepatocellular carcinoma from WA Data Linkage Unit databases. Competing risk analysis was used to calculate the cumulative risk of each clinical endpoint, and risks for clinical endpoints were compared among all causes of chronic liver disease. RESULTS In our final cohort for analysis, 5566 patients had hepatitis C virus (HCV) infection, 1989 had HBV infection, 119 were infected with HBV and HCV, 955 had alcohol-associated liver disease, 1597 had non-alcoholic fatty liver disease (NAFLD), 123 had alcohol-associated liver disease and metabolic risk factors, 561 had autoimmune liver disease without overlap syndrome, and 23 autoimmune overlap syndrome. Significant differences among chronic liver diseases were observed in risk of all-cause death (P < .001), liver-related death (P < .001), liver transplantation (P < .001), and decompensation (P < .001) but not hepatocellular carcinoma (P=.095). Patients with alcohol-associated liver disease had the highest 5-year cumulative risk of liver-related death (17.1%) and the second-highest 5-year cumulative risk of decompensation (29.2%). Multivariate analysis found patients with alcohol-associated liver disease had significantly higher risks of liver-related death and decompensation than patients with HCV infection with hazard ratios (HRs) of 2.39 (95% CI, 1.88-3.03) and 3.42 (95% CI, 2.74-4.27), respectively. Patients with NAFLD had a significantly lower risk of liver related death and decompensation than patients with HCV infection, with HRs of 0.67 (95% CI, 0.48-0.95) and 0.70 (95% CI, 0.52-0.94) respectively. CONCLUSIONS In an analysis of patients in Western Australia, we found patients with alcohol-associated liver disease to have significantly higher risk of decompensation and liver-related death than patients with HCV infection, whereas patients with NAFLD have significantly lower risks of either outcome.
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Affiliation(s)
- Yi Huang
- School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - John Joseph
- Department of Biochemistry, PathWest Laboratory Medicine, Perth, Australia
| | - W Bastiaan de Boer
- Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, Australia
| | - Wendy Cheng
- Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Australia
| | - Leon A Adams
- School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Gerry MacQuillan
- School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - George Garas
- School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Spiro Raftopoulos
- Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Gary P Jeffrey
- School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Hepatology, Sir Charles Gairdner Hospital, Perth, Australia.
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Likhitsup A, Dundulis J, Ansari S, Patibandla S, Hutton C, Kennedy K, Helzberg JH, Chhabra R. High prevalence of non-alcoholic fatty liver disease in patients with inflammatory bowel disease receiving anti-tumor necrosis factor therapy. Ann Gastroenterol 2019; 32:463-468. [PMID: 31474792 PMCID: PMC6686093 DOI: 10.20524/aog.2019.0405] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Accepted: 06/25/2019] [Indexed: 02/07/2023] Open
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is common in patients with inflammatory bowel disease (IBD). This study evaluated the prevalence of NAFLD and the associated risk factors among IBD patients who received anti-tumor necrosis factor (TNF) therapy. Methods: Adult IBD patients receiving anti-TNF therapy (infliximab, adalimumab, certolizumab, golimumab) were enrolled. Hepatic steatosis was assessed by abdominal ultrasound. Patients with a history of excessive alcohol or recent steroid use were excluded. Univariate and multivariate analysis were performed. Results: Eighty patients, 55% male, mean age 42±15 years, were enrolled. The sonographic prevalence of NAFLD was 54% (43/80), significantly higher than the general prevalence in the US adult population (30%) (P<0.0001). NAFLD patients had a significantly higher proportion of males, as well as greater body weight and body mass index, compared to non-NAFLD. The Crohns disease activity index (CDAI) was significantly higher among patients with NAFLD. Multivariate analysis demonstrated that a higher CDAI was independently associated with NAFLD, with an odds ratio of 1.6 (95% confidence interval 1.05-2.44; P=0.03). Conclusions: The presence of IBD is strongly associated with NAFLD. We identified a high prevalence of NAFLD among IBD patients receiving anti-TNF. CDAI was independently associated with hepatic steatosis. Further studies are still needed to evaluate the pathophysiology of NAFLD development and disease progression among IBD populations.
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Affiliation(s)
- Alisa Likhitsup
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Jason Dundulis
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Shaya Ansari
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Sruthi Patibandla
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra)
| | - Colleen Hutton
- Mid-America Heart Institute St. Luke's Health System (Colleen Hutton, Kevin Kennedy), Kansas City, MO, USA
| | - Kevin Kennedy
- Mid-America Heart Institute St. Luke's Health System (Colleen Hutton, Kevin Kennedy), Kansas City, MO, USA
| | - John H Helzberg
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Rajiv Chhabra
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
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19
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Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation. Transplantation 2019; 103:22-27. [PMID: 30335697 DOI: 10.1097/tp.0000000000002484] [Citation(s) in RCA: 261] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population with a range of 13.5% in Africa and 31.8% in the Middle East. Nonalcoholic fatty liver disease is closely associated with a constellation of metabolic comorbidities which include: obesity, type 2 diabetes mellitus, hypertension, and hypercholesteremia. In fact, the increasing number of metabolic comorbidities not only increases the prevalence of NAFLD but also places patients at higher risk for progressive liver disease. As such, NAFLD is presently among the top etiologies for hepatocellular carcinoma and an indication for liver transplantation (LT) in the United States. Therefore, the following recommendations are made based on our current knowledge of NAFLD and its consequences: (1) the evaluation of the risk of liver disease progression can be affected by patient's ethnic origin and sex; (2) fibrosis in NAFLD is the most important predictor of mortality; (3) we recommend that individuals who present with features of metabolic syndrome in the presence of elevated liver enzymes should be screened for NAFLD and, more importantly, nonalcoholic steatohepatitis (NASH); (4) we recommend that NAFLD patients, especially those with multiple risk factors, should be screened for cardiovascular diseases and managed accordingly; (5) comorbidities in NAFLD/NASH patients who are considered for LT need to be assessed in the pretransplant and posttransplant settings because these factors can affect waitlist mortality, resource utilization, as well as posttransplant complications, morbidity, and perhaps, mortality; (6) any attempt to decrease the incidence of NAFLD should ideally address the development of obesity in childhood and early adulthood, favoring the adoption of healthy lifestyles through comprehensive health policy programs.
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20
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly dominant cause of liver disease worldwide. The progressive subtype, nonalcoholic steatohepatitis, is a leading indication for liver transplantation and a noteworthy cause of hepatocellular carcinoma. The overall prevalence of NAFLD is on the rise, and even more concerning data modeling predicts that an increasing percentage of those with NAFLD will develop advanced disease. This increased volume of patients with advanced liver disease will impose a significant health care burden in terms of resources and cost. Thus, the identification of patients with established fibrosis or at high risk of developing advanced liver disease is critical to effectively intervene and prevent overall and liver-related morbidity and mortality. Herein, we provide a framework to consider for the identification of patients with NAFLD at high risk of nonalcoholic steatohepatitis with advanced fibrosis and provide a critical assessment of currently accessible diagnostic and treatment modalities.
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21
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Likhitsup A, Dundulis J, Ansari S, El-Halawany H, Michelson R, Hutton C, Kennedy K, Helzberg JH, Chhabra R. Prevalence of non-alcoholic fatty liver disease on computed tomography in patients with inflammatory bowel disease visiting an emergency department. Ann Gastroenterol 2019; 32:283-286. [PMID: 31040626 PMCID: PMC6479650 DOI: 10.20524/aog.2019.0371] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 02/01/2019] [Indexed: 12/13/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is common in patients with inflammatory bowel disease (IBD). The purpose of this study was to further examine the prevalence of NAFLD in IBD patients. Methods We retrospectively reviewed the medical records of IBD patients who visited the emergency department because of abdominal pain between January 2009 and December 2014. These were compared with a group of 70 controls without IBD, matched for age and body mass index (BMI). Computed tomography data were analyzed for the presence or absence of hepatic steatosis. Patient with recent steroid or excessive alcohol use were excluded. Univariate and multivariate analyses were performed. Results NAFLD prevalence was 44% (31/70) in the IBD group vs. 16% (11/70) in controls (P<0.001). There was no significant difference between the 2 groups in age, sex distribution, BMI, presence of diabetes, or levels of serum transaminases, serum albumin or platelets. In multivariate analysis, the presence of IBD was independently associated with NAFLD (odds ratio 4.53, 95% confidence interval 2.00-10.26; P=0.002). Conclusions The presence of IBD is strongly and independently associated with NAFLD. Systemic inflammation and alteration of the intestinal microbiome have been proposed as mechanisms, but further studies are needed to better elucidate the pathophysiology.
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Affiliation(s)
- Alisa Likhitsup
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra).,Department of Gastroenterology and Hepatology, Saint Luke's Hospital of Kansas City (Alisa Likhitsup, John H. Helzberg, Rajiv Chhabra)
| | - Jason Dundulis
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra)
| | - Shaya Ansari
- Department of Radiology, University of Missouri Kansas City (Shaya Ansari)
| | - Hani El-Halawany
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra)
| | - Randal Michelson
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra)
| | - Colleen Hutton
- Department of Clinical Research, Mid-America Heart Institute St. Luke's Health System (Colleen Hutton)
| | - Kevin Kennedy
- Department of Biostatistics, Mid-America Heart Institute St. Luke's Health System (Kevin Kennedy), Kansas City, MO, USA
| | - John H Helzberg
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra).,Department of Gastroenterology and Hepatology, Saint Luke's Hospital of Kansas City (Alisa Likhitsup, John H. Helzberg, Rajiv Chhabra)
| | - Rajiv Chhabra
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra).,Department of Gastroenterology and Hepatology, Saint Luke's Hospital of Kansas City (Alisa Likhitsup, John H. Helzberg, Rajiv Chhabra)
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22
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Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism 2019; 92:82-97. [PMID: 30502373 DOI: 10.1016/j.metabol.2018.11.014] [Citation(s) in RCA: 758] [Impact Index Per Article: 126.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 11/24/2018] [Accepted: 11/24/2018] [Indexed: 02/06/2023]
Abstract
The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with simple steatosis (SS), but also with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. As a consequence, apart from increasing all-cause mortality, obesity seems to increase liver-specific mortality in NAFLD patients. Given the lack of approved pharmacological interventions for NAFLD, targeting obesity is a rational option for its management. As the first step, lifestyle modification (diet and exercise) is recommended, although it is difficult to achieve and sustain. When the first step fails, adding pharmacotherapy is recommended. Several anti-obesity medications have been investigated in NAFLD (e.g., orlistat, glucagon-like peptide-1 analogs), other anti-obesity medications have not been investigated (e.g., lorcaserin, phentermine hydrochloric, phentermine/topiramate and naltrexone/bupropion), whereas some medications with weight-lowering efficacy have not been approved for obesity (e.g., sodium-glucose cotransporter-2 inhibitors, farnesoid X receptor ligands). If the combination of lifestyle modification and pharmacotherapy also fails, then bariatric surgery should be considered in selected morbidly obese individuals. This review summarizes best evidence linking obesity with NAFLD and presents related therapeutic options.
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Affiliation(s)
- Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Jannis Kountouras
- Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece
| | - Christos S Mantzoros
- Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA
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23
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Younossi ZM. Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol 2019; 70:531-544. [PMID: 30414863 DOI: 10.1016/j.jhep.2018.10.033] [Citation(s) in RCA: 1389] [Impact Index Per Article: 231.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/24/2018] [Accepted: 10/30/2018] [Indexed: 12/04/2022]
Abstract
As the epidemics of obesity and type 2 diabetes mellitus increase worldwide, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing proportionately. The subtype of NAFLD which can be characterised as non-alcoholic steatohepatitis (NASH) is a potentially progressive liver disease that can lead to cirrhosis, hepatocellular carcinoma, liver transplantation, and death. NAFLD is also associated with extrahepatic manifestations such as chronic kidney disease, cardiovascular disease and sleep apnoea. NAFLD and NASH carry a large economic burden and create poor health-related quality of life. Despite this important burden, we are only beginning to understand its mechanisms of pathogenesis and the contribution of environmental and genetic factors to the risk of developing a progressive course of disease. Research is underway to identify appropriate non-invasive diagnostic methods and effective treatments. Although the risk of liver-related mortality is increased in patients with NAFLD and liver fibrosis stages F3 or F4, the leading cause of death is cardiovascular disease. Given the rapidly growing global burden of NAFLD and NASH, efforts must continue to find accurate non-invasive diagnostic and prognostic biomarkers, to develop effective treatments for individuals with advanced NASH and prevention methods for individuals at high risk of NAFLD and progressive liver disease.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
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24
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Lam B, Kurzke K, Younossi Z. The Clinical and Economic Burden of Nonalcoholic Steatohepatitis. ACTA ACUST UNITED AC 2018. [DOI: 10.1007/s11901-018-0423-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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25
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Lu FB, Hu ED, Xu LM, Chen L, Wu JL, Li H, Chen DZ, Chen YP. The relationship between obesity and the severity of non-alcoholic fatty liver disease: systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2018; 12:491-502. [PMID: 29609501 DOI: 10.1080/17474124.2018.1460202] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
A number of researches have explored the association between obesity and nonalcoholic fatty liver disease (NAFLD) liver function, histopathology, complications, genetic factors and prognosis, but the results were conflicting and inconclusive. Areas covered: In this meta-analysis, the liver function, histopathology, metabolic complications, patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic polymorphism and prognosis were compared between non-obese and obese NAFLD. Pubmed, EMBASE, Cochrane databases were searched to identify eligible studies. The odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) were pooled using fixed- or random-effects models. Expert commentary: This meta-analysis indicated that for NAFLD patients, obesity (according to ethnic-specific BMI cut-off points to define obesity) could predict a worse long-term prognosis. However, obesity may not be an independent factor for the development of NASH or advanced fibrosis in NAFLD patients and NAFLD should be considered as potential population for pharmacologic treatment regardless of obesity. In addition, PNPLA3 rs738409 may be more relevant to the progression of non-obese NAFLD when compared to obese NAFLD. Importantly, large-sample, long-term follow-up cohort studies based on liver biopsy are highly needed due to limited liver pathology and long-term follow-up data at present.
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Affiliation(s)
- Feng-Bin Lu
- a Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology , Wenzhou , China
| | - En-De Hu
- a Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology , Wenzhou , China
| | - Lan-Man Xu
- a Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology , Wenzhou , China
| | - Lu Chen
- a Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology , Wenzhou , China
| | - Jin-Lu Wu
- a Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology , Wenzhou , China
| | - Hui Li
- a Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology , Wenzhou , China
| | - Da-Zhi Chen
- b State Key Laboratory of Infectious Diseases , Medicine School of Zhejiang University , Hangzhou , China
| | - Yong-Ping Chen
- a Department of Infectious Diseases , the First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology , Wenzhou , China
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Golabi P, Stepanova M, Pham HT, Cable R, Rafiq N, Bush H, Gogoll T, Younossi ZM. Non-alcoholic steatofibrosis (NASF) can independently predict mortality in patients with non-alcoholic fatty liver disease (NAFLD). BMJ Open Gastroenterol 2018; 5:e000198. [PMID: 29607054 PMCID: PMC5873539 DOI: 10.1136/bmjgast-2018-000198] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 02/28/2018] [Accepted: 03/02/2018] [Indexed: 01/03/2023] Open
Abstract
Background Hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) independently predicts mortality. Given liver biopsy’s invasive nature, non-invasive method to assess hepatic steatosis and fibrosis provides NAFLD risk stratification algorithm in clinical practice. NAFLD fibrosis score (NFS) is simple and non-invasive predictive model recommended by American Association for the Study of Liver Disease (AASLD) Guideline to identify patients with NAFLD with fibrosis risk. The aim of this study is to assess long-term outcomes of subjects with significant non-alcoholic steatofibrosis (NASF) as established by ultrasound (US) and NFS. Methods Used National Health and Nutrition Examination Survey (NHANES III) with National Death Index-linked Mortality Files. NAFLD diagnosis established by the presence of moderate to severe hepatic steatosis on US without other causes of chronic liver disease (alcohol consumption <20 gr/day, hepatitis B surface-antigen negative, anti-hepatitis C virus antibody negative, transferrin saturation <50%). Significant hepatic fibrosis was estimated by high NFS (>0.676) and calculated with previously published formula. Subjects with NAFLD and high NFS have significant NASF. Results NHANES III included 20 050 adult participants. 2515 participants complete data and NAFLD with 5.1% (n=129) meeting criteria for significant SF. Subjects with significant SF were older, had higher body mass index, waist circumference and the homeostasis model assessment (HOMA) scores and higher rates of comorbidities (diabetes, congestive heart failure (CHF), stroke; all p<0.001). After median of 207 months of follow-up, overall mortality in NAFLD cohort was 30.0% (n=754). Crude mortality higher in subjects with significant SF (67.4% vs 28.0%, p<0.001). In multivariate survival analysis, predictors of overall mortality included significant SF (adjusted HR (aHR): 1.37; 95% CI 1.07 to 1.76, p=0.01), older age (aHR:1.08; 95% CI 1.07 to 1.09 per year), male gender (aHR:1.44; 95% CI 1.24 to 1.67), black race (aHR:1.24; 95% CI 1.04 to 1.48)), history of hypertension (aHR:1.40; 95% CI 1.20 to 1.64), diabetes (aHR:1.69; 95% CI 1.43 to 2.00), CHF (aHR:1.77; 95% CI 1.38 to 2.261), stroke (aHR:1.84; 95% CI 1.38 to 2.48) and smoking (aHR:1.74; 95% CI 1.47 to 2.07) (all p<0.02). Sensitivity analysis showed that the best association of SF with mortality is higher at NFS threshold of 0.80 (aHR:1.41; 95% CI 1.09 to 1.83, p=0.01). Conclusions Significant NASF determined non-invasively is an independent predictor of mortality. These data should help clinicians to easily risk-stratify patients with NAFLD for close monitoring and treatment considerations in clinical trial setting.
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Affiliation(s)
- Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Columbia, Washington, USA
| | - Huong T Pham
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
| | - Rebecca Cable
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
| | - Nila Rafiq
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.,Department of Medicine, Center For Liver Disease, Inova Fairfax Hospital, Falls Church, Virginia, USA
| | - Haley Bush
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
| | - Trevor Gogoll
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
| | - Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA.,Department of Medicine, Center For Liver Disease, Inova Fairfax Hospital, Falls Church, Virginia, USA
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27
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Golabi P, Otgonsuren M, de Avila L, Sayiner M, Rafiq N, Younossi ZM. Components of metabolic syndrome increase the risk of mortality in nonalcoholic fatty liver disease (NAFLD). Medicine (Baltimore) 2018; 97:e0214. [PMID: 29595666 PMCID: PMC5895395 DOI: 10.1097/md.0000000000010214] [Citation(s) in RCA: 151] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. Metabolic syndrome (MS) components are highly prevalent in NAFLD. Our aim is to assess the relationship of NAFLD and MS with long-term outcome of mortality.The Third National Health and Nutrition Examination Survey (NHANES) was utilized. NAFLD was diagnosed by ultrasound in the presence of hepatic steatosis and no other causes of chronic liver disease. History of MS and its components were obtained from self-reported NHANES questionnaires. Mortality was obtained from Mortality-Linkage File, through December 31, 2011. Chi-square test was used for categorical variables and Cox proportional models estimated hazard ratios with 95% confidence interval.NAFLD cohort (n = 3613) had a median age of 43 years, 73% white, and 50% male. NAFLD group with at least one MS condition was significantly older, had higher body mass index, more likely to have insulin resistance, and heart disease compared to NAFLD group without MS. Over 19-years of follow-up, 1039 people died. Compared to NAFLD patients without MS, presence of one MS component increased the risk of mortality at 8-year (2.6% vs 4.7%) and 16-year (6% vs 11.9%) (P < .001). After adjusting for socio-demographic factors, NAFLD with all MS components was associated with overall, cardiac and liver-mortality. Increased number of MS components was associated with lower survival (P < .0001).Patients with NAFLD and MS have higher mortality risk compared to NAFLD patients without MS. These NAFLD patients should be prioritized for the development of treatment regimens.
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Affiliation(s)
- Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
| | | | - Leyla de Avila
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
| | - Mehmet Sayiner
- Center for Liver Disease, Department of Medicine, Inova Fair, Falls Church, VA
| | - Nila Rafiq
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
- Center for Liver Disease, Department of Medicine, Inova Fair, Falls Church, VA
| | - Zobair M. Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System
- Center for Liver Disease, Department of Medicine, Inova Fair, Falls Church, VA
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Younossi ZM, Henry L, Bush H, Mishra A. Clinical and Economic Burden of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Clin Liver Dis 2018; 22:1-10. [PMID: 29128049 DOI: 10.1016/j.cld.2017.08.001] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with an increasing global prevalence associated with tremendous clinical, economic, and health-related quality-of-life burden. Clinically, NAFLD is considered the liver manifestation of metabolic syndrome. However, diagnosing NAFLD presents significant challenges due to the limited noninvasive and accurate diagnostic tools available to not only accurately diagnose nonalcoholic steatohepatitis but also to stage hepatic fibrosis, the major predictor of long-term outcomes, including mortality.
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Affiliation(s)
- Zobair M Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA.
| | - Linda Henry
- Center for Outcomes Research in Liver Disease, 2411 I Street NW, Washington, DC 20037, USA
| | - Haley Bush
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA
| | - Alita Mishra
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA
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29
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Akhavan Rezayat A, Dadgar Moghadam M, Ghasemi Nour M, Shirazinia M, Ghodsi H, Rouhbakhsh Zahmatkesh MR, Tavakolizadeh Noghabi M, Hoseini B, Akhavan Rezayat K. Association between smoking and non-alcoholic fatty liver disease: A systematic review and meta-analysis. SAGE Open Med 2018; 6:2050312117745223. [PMID: 29399359 PMCID: PMC5788091 DOI: 10.1177/2050312117745223] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 10/16/2017] [Indexed: 12/17/2022] Open
Abstract
Background/aims Non-alcoholic fatty liver disease is one of the most common chronic liver diseases. Some risk factors are known to influence the development of non-alcoholic fatty liver disease, but the effect of tobacco smoking on the progression of non-alcoholic fatty liver disease is controversial. The main goal of this systematic review and meta-analysis is to investigate the association between smoking and non-alcoholic fatty liver disease. Method Electronic databases (PubMed, Scopus, and ISI Web of Science) were searched to find published articles on non-alcoholic fatty liver disease and smoking until December 2016. All relevant studies were screened by inclusion and exclusion criteria and compatible studies were chosen. The Newcastle-Ottawa Scale was used to assess the methodological quality of eligible articles. Subsequently, information was gathered based on the following: author, publication year, keywords, country, inclusion and exclusion criteria, main results, study design, conclusion, and confounder variables (age, body mass index, gender, ethnicity, and diabetes). Finally, analyses were performed using Comprehensive Meta-Analysis Software. Results Data were extracted from 20 observational studies (9 cross-sectional, 6 case-control, 4 cohort studies, and 1 retrospective cohort study). A significant association was observed between smoking and non-alcoholic fatty liver disease with a pooled odds ratio of 1.110 (95% confidence interval, 1.028-1.199), p-value = 0.008. The statistical heterogeneity was medium with an I2 of 40.012%, p-heterogeneity = 0.074. Also there was a significant relation between non-alcoholic fatty liver disease and passive smoking with a pooled odds ratio of 1.380 (95% confidence interval, 1.199-1.588; p-value = 0.001; I2 = 59.41; p-heterogeneity = 0.117). Conclusion Our meta-analysis demonstrated that smoking is significantly associated with non-alcoholic fatty liver disease. Further prospective studies exploring the underlying mechanisms of this association should be pursued. Also passive smoking increases the risk of non-alcoholic fatty liver disease about 1.38-fold. The effects of smoking cigarettes on active smokers (current smoker, former smoker, and total smoker) are less than passive smokers. Further studies are needed to compare the of effects of passive and active smoking on non-alcoholic fatty liver disease.
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Affiliation(s)
- Arash Akhavan Rezayat
- Gastroenterology and Hepatology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Malihe Dadgar Moghadam
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ghasemi Nour
- Gastroenterology and Hepatology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Matin Shirazinia
- Gastroenterology and Hepatology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamidreza Ghodsi
- Gastroenterology and Hepatology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Rouhbakhsh Zahmatkesh
- Gastroenterology and Hepatology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Benyamin Hoseini
- Gastroenterology and Hepatology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kambiz Akhavan Rezayat
- Gastroenterology and Hepatology Research Center, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
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30
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Khalil A, Cevik SE, Hung S, Kolla S, Roy MA, Suvorov A. Developmental Exposure to 2,2',4,4'-Tetrabromodiphenyl Ether Permanently Alters Blood-Liver Balance of Lipids in Male Mice. Front Endocrinol (Lausanne) 2018; 9:548. [PMID: 30294300 PMCID: PMC6158338 DOI: 10.3389/fendo.2018.00548] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 08/29/2018] [Indexed: 12/21/2022] Open
Abstract
Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives starting 1965 and were recently withdrawn from commerce in North America and Europe. Approximately 1/5 of the total U.S. population were born when environmental concentrations of PBDE plateaued at their maximum. Accumulating evidence suggests that developmental exposures to PBDE may result in long-lasting programming of liver metabolism. In this study, CD-1 mice were exposed prenatally or neonatally to 1 mg/kg body weight of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), and changes in liver histology, transcriptome, and liver-blood balance of triglycerides were analyzed in 10 months old male offspring. In both exposure groups, long-term reprogramming of lipid metabolism was observed, including increased liver triglycerides and decreased blood triglycerides, and altered expression of metabolic genes in the liver. Significant upregulation of lipid influx transporter Cd36 2.3- and 5.7-fold in pre- and neonatal exposure groups, respectively was identified as a potential mechanism of blood/liver imbalance of triglycerides. Analysis of our and previously published all-genome gene expression data identified changes in expression of ribosomal protein genes as a transcriptomic signature of PBDE exposure. Further comparison of our new data and published data demonstrate that low doses (0.2 mg/kg body weight) of PBDE induce long-lasting up-regulation of ribosomal genes, suppression of Cd36 in liver and increase circulating triglycerides in blood, while moderated doses (≥1 mg/kg body weight) produce opposite long-lasting effects. To conclude, this study shows that an environmentally relevant developmental exposures to BDE-47 permanently alter lipid uptake and accumulation in the liver, with low and moderate doses having opposite effect on liver transcriptomics and triglyceride balance. Similar effects of pre- and neonatal exposures point at hepatocyte maturation as a sensitive window of the liver metabolism programming. These results suggest that PBDE exposure may be an important factor increasing risks of cardio-vascular disease and non-alcoholic fatty liver disease via modulation of liver/blood balance of lipids. The translational relevance of these findings for human remain to be studied.
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Affiliation(s)
- Ahmed Khalil
- Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States
- Medical Biotechnology Department, Genetic Engineering & Biotechnology Research Institute, City of Scientific Research & Technological Applications, Alexandria, Egypt
| | - Sebnem E. Cevik
- Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States
| | - Stephanie Hung
- Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States
| | - Sridurgadevi Kolla
- Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States
| | - Monika A. Roy
- Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States
| | - Alexander Suvorov
- Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States
- *Correspondence: Alexander Suvorov
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31
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Greuter T, Malhi H, Gores GJ, Shah VH. Therapeutic opportunities for alcoholic steatohepatitis and nonalcoholic steatohepatitis: exploiting similarities and differences in pathogenesis. JCI Insight 2017; 2:95354. [PMID: 28878132 DOI: 10.1172/jci.insight.95354] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are among the most frequent causes of chronic liver disease in the United States. Although the two entities are triggered by different etiologies - chronic alcohol consumption (ASH) and obesity-associated lipotoxicity (NASH) - they share overlapping histological and clinical features owing to common pathogenic mechanisms. These pathogenic processes include altered hepatocyte lipid metabolism, organelle dysfunction (i.e., ER stress), hepatocyte apoptosis, innate immune system activation, and hepatic stellate cell activation. Nonetheless, there are several disease-specific molecular signaling pathways, such as differential pathway activation downstream of TLR4 (MyD88-dependence in NASH versus MyD88-independence in ASH), inflammasome activation and IL-1β signaling in ASH, insulin resistance and lipotoxicity in NASH, and dysregulation of different microRNAs, which clearly highlight that ASH and NASH are two distinct biological entities. Both pathogenic similarities and differences have therapeutic implications. In this Review, we discuss these pathogenic mechanisms and their therapeutic implications for each disease, focusing on both shared and distinct targets.
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Affiliation(s)
- Thomas Greuter
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.,Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Harmeet Malhi
- Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Gregory J Gores
- Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Vijay H Shah
- Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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32
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Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases. Clin Res Hepatol Gastroenterol 2017; 41:31-38. [PMID: 27597641 DOI: 10.1016/j.clinre.2016.07.005] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 04/15/2016] [Accepted: 07/18/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS The association between cardiovascular diseases (CVD) and non-alcoholic fatty liver disease (NAFLD) was confirmed by a large body of evidence. This study was conducted to determine the association between NAFLD and 10-year CVD risk. METHODS This study utilized the data of 2804 subjects aged 40-74 years from a cohort study of northern Iran. Two CVD risk assessment tools, American College of Cardiology/American Heart Association and Framingham general cardiovascular risk profile for use in primary care, were utilized to determine the 10-year CVD risk in patients with NAFLD and the individuals without this condition. The mean risks were compared between these two groups. RESULTS Using ACC/AHA approach, the mean risk in male participants suffering NAFLD was 14.2%, while in men without NAFLD was 11.7% (P-value < 0.0001). Using Framingham approach, the mean risks were 16.0 and 12.7% in men with and without NAFLD, respectively (P-value < 0.0001). Using ACC/AHA approach, the mean risks in female participants with and without NAFLD were 6.7 and 4.6%, respectively (P-value < 0.0001). Applying Framingham approach, the mean risk was 8.2% in women with NAFLD and 5.4% in women without NAFLD (P-value < 0.0001). CONCLUSION The individuals with NAFLD had a higher risk of 10-year CVD events than individuals without NAFLD, according to both ACC/AHA tool and primary care version of Framingham tool. A large proportion of NAFLD patients fulfill the criteria of statin therapy recommendation, suggesting that statin therapy could reduce 10-year CVD risk in NAFLD patients.
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Younossi ZM, Blissett D, Blissett R, Henry L, Stepanova M, Younossi Y, Racila A, Hunt S, Beckerman R. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology 2016; 64:1577-1586. [PMID: 27543837 DOI: 10.1002/hep.28785] [Citation(s) in RCA: 883] [Impact Index Per Article: 98.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 08/02/2016] [Indexed: 02/06/2023]
Abstract
UNLABELLED Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady-state prevalence model to quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incidence and remission rates were calculated by calibrating against real-world prevalence rates. The data were validated using a computerized disease model called DisMod II. NAFLD patients transitioned between nine health states (nonalcoholic fatty liver, nonalcoholic steatohepatitis [NASH], NASH-fibrosis, NASH-compensated cirrhosis, NASH-decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, post-liver transplant, and death). Transition probabilities were sourced from the literature and calibrated against real-world data. Utilities were obtained from NAFLD patients using the Short Form-6D. Costs were sourced from the literature and local fee schedules. In the United States, over 64 million people are projected to have NAFLD, with annual direct medical costs of about $103 billion ($1,613 per patient). In the Europe-4 countries (Germany, France, Italy, and United Kingdom), there are ∼52 million people with NAFLD with an annual cost of about €35 billion (from €354 to €1,163 per patient). Costs are highest in patients aged 45-65. The burden is significantly higher when societal costs are included. CONCLUSION The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577-1586).
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA.
| | | | | | - Linda Henry
- Center for Outcomes Research in Liver Disease, Washington, DC
| | - Maria Stepanova
- Center for Outcomes Research in Liver Disease, Washington, DC
| | | | - Andrei Racila
- Center for Outcomes Research in Liver Disease, Washington, DC
| | - Sharon Hunt
- Betty and Guy Beatty Center for Integrated Research, Inova Health Systems, Falls Church, VA
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Yun KE, Nam GE, Lim J, Park HS, Chang Y, Jung HS, Kim CW, Ko BJ, Chung EC, Shin H, Ryu S. Waist Gain Is Associated with a Higher Incidence of Nonalcoholic Fatty Liver Disease in Korean Adults: A Cohort Study. PLoS One 2016; 11:e0158710. [PMID: 27420035 PMCID: PMC4946777 DOI: 10.1371/journal.pone.0158710] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 06/21/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We examined the relationship between changes in waist circumference (WC) and the incidence of nonalcoholic fatty liver disease (NAFLD). METHODS A cohort study of 37,130 men and women were followed-up annually or biennially. Differences in WC between baseline and subsequent measurements were categorized in quartiles: first (WC loss), second (no change in WC as the reference), third and highest quartiles (WC gain). The presence of fatty liver was determined using ultrasound. Parametric Cox modeling was used to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) of the incidence of NAFLD. RESULTS During 127,324.4 person-years of follow-up, 6249 participants developed NAFLD. Despite adjusting for possible confounders, the risk of development of NAFLD increased with increasing quartiles of WC change in a dose-response manner (p for trend < 0.001). Compared with the reference, WC loss was associated with a lower risk of NAFLD (men: aHR 0.79 [95% CI: 0.73-0.87]; women: 0.72 [0.63-0.81]), and the highest quartile (WC gain) was associated with a higher risk of NAFLD (men: 1.30 [1.19-1.42]; women: 1.48 [1.31-1.67]). CONCLUSION Waist gain appears to increase the risk of developing NAFLD, independently of the baseline body mass index and WC.
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Affiliation(s)
- Kyung Eun Yun
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Ga Eun Nam
- Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan-si, South Korea
| | - Jisun Lim
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hye Soon Park
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Hyun-Suk Jung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Chan-Won Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Byung-Joon Ko
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Eun Chul Chung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea
| | - Hocheol Shin
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
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Motamed N, Maadi M, Sohrabi M, Keyvani H, Poustchi H, Zamani F. Rural Residency has a Protective Effect and Marriage is a Risk Factor for NAFLD. HEPATITIS MONTHLY 2016; 16:e38357. [PMID: 27642349 PMCID: PMC5018359 DOI: 10.5812/hepatmon.38357] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/17/2016] [Revised: 05/07/2016] [Accepted: 05/22/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is considered the leading cause of liver disease worldwide. Although many previous studies have evaluated the potential risk factors of NAFLD, few studies have determined the effect of residency or marriage status on NAFLD. OBJECTIVES We aim to evaluate whether residency and marriage status increased the risk factors for NAFLD. MATERIALS AND METHODS We utilized data from 5,052 participants, 18 years and older, from a cohort study conducted using 6,140 participants in northern Iran. The population was divided into 16 subgroups according to sex and age; the age groups had an interval of 10 years. We randomly selected the subjects from each subgroup in proportion to the size of each subpopulation group. Logistic regression analyses were conducted on NAFLD as an outcome of marriage status, residency (rural vs. urban), and other potential risk factors. RESULTS We found that NAFLD had an inverse association with rural living in men (OR = 0.513, 0.422 - 0.622, P value < 0.001) and women (OR = 0.431, 0.345 - 0.539, P value < 0.001). Furthermore, we determined that NAFLD had a direct association with marriage status for men (OR = 2.770, 2.004 - 3.831, P value < 0.001) and women (OR = 1.241, 1.033 - 1.490, P value = 0.0209). CONCLUSIONS While rural living has a protective effect on NAFLD, marriage may be a potential risk factor for this condition.
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Affiliation(s)
- Nima Motamed
- Gastrointestinal and Liver Disease Research Centre, Iran University of Medical Sciences, Tehran, IR Iran
| | - Mansooreh Maadi
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, IR Iran
| | - Masoudreza Sohrabi
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, IR Iran
| | - Hossein Keyvani
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, IR Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Farhad Zamani
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, IR Iran
- Corresponding Author: Farhad Zamani, Gastrointestinal and Liver Disease Research Centre, Iran University of Medical Sciences, Tehran, IR Iran. Tel: +98-2182141303, E-mail:
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Younossi Z, Henry L. Contribution of Alcoholic and Nonalcoholic Fatty Liver Disease to the Burden of Liver-Related Morbidity and Mortality. Gastroenterology 2016; 150:1778-85. [PMID: 26980624 DOI: 10.1053/j.gastro.2016.03.005] [Citation(s) in RCA: 239] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Revised: 02/15/2016] [Accepted: 03/02/2016] [Indexed: 12/15/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. NAFLD is associated with obesity and metabolic syndrome whereas ALD is associated with excessive alcohol consumption. Both diseases can progress to cirrhosis, hepatocellular carcinoma, and liver-related death. A higher proportion of patients with NAFLD die from cardiovascular disorders than patients with ALD, whereas a higher proportion of patients with ALD die from liver disease. NAFLD and ALD each are associated with significant morbidity, impairment to health-related quality of life, and economic costs to society.
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Affiliation(s)
- Zobair Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
| | - Linda Henry
- Center for Outcomes Research in Liver Diseases, Washington, District of Columbia
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Pang Q, Zhang JY, Song SD, Qu K, Xu XS, Liu SS, Liu C. Central obesity and nonalcoholic fatty liver disease risk after adjusting for body mass index. World J Gastroenterol 2015; 21:1650-1662. [PMID: 25663786 PMCID: PMC4316109 DOI: 10.3748/wjg.v21.i5.1650] [Citation(s) in RCA: 133] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Revised: 06/11/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether central obesity is associated with nonalcoholic fatty liver disease (NAFLD) formation after adjusting for general obesity.
METHODS: The online databases PubMed, EMBASE, and ISI Web of Science were searched for studies estimating the influence of central obesity on NAFLD occurrence published through April 2014. Studies that did not adjust for body mass index (BMI) were excluded. In addition, the independent effect of BMI was also assessed with the included studies. The pooled effect sizes and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the degree of heterogeneity. Furthermore, subgroup analyses, meta-regression, sensitivity analyses, and publication bias were performed.
RESULTS: Twenty eligible studies were identified. The summary odds ratio (OR) values per-unit increase in waist circumference (WC) and BMI for NAFLD formation were 1.07 (95%CI: 1.03-1.10, I2 = 73.9%, n = 11 studies) and 1.25 (95%CI: 1.13-1.38, I2 = 88.7%, n = 11 studies), respectively. When the indices were expressed as binary variables (with the non-obesity group as reference), the pooled OR in WC, waist-to-hip ratio, and BMI were 2.34 (95%CI: 1.83-3.00, I2 = 41.8%, n = 7 studies), 4.06 (95%CI: 1.53-10.79, I2 = 65.7%, n = 3 studies), and 2.85 (95%CI: 1.60-5.08, I2 = 57.8%, n = 5 studies), respectively. Using the same studies as the latter (n = 5), pooled OR in WC was 3.14 (95%CI: 2.07-4.77), which is greater than that in BMI.
CONCLUSION: Central obesity may pose a greater threat to national health than general obesity, although both are independently associated with increased risk of NAFLD.
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Suomela E, Oikonen M, Virtanen J, Parkkola R, Jokinen E, Laitinen T, Hutri-Kähönen N, Kähönen M, Lehtimäki T, Taittonen L, Tossavainen P, Jula A, Loo BM, Mikkilä V, Younossi Z, Viikari JSA, Juonala M, Raitakari OT. Prevalence and determinants of fatty liver in normal-weight and overweight young adults. The Cardiovascular Risk in Young Finns Study. Ann Med 2015; 47:40-6. [PMID: 25333756 DOI: 10.3109/07853890.2014.966752] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND AND AIMS Fatty liver may have different determinants in normal-weight and in obese individuals. We measured factors associated with fatty liver in 863 normal-weight (BMI < 25) and 1135 overweight/obese (BMI ≥ 25) young and middle-aged adults (45% male, age 34-49 years) in the population-based Cardiovascular Risk in Young Finns Study. METHODS AND RESULTS The prevalence of fatty liver detected with ultrasound was 29% in overweight/obese and 5% in normal-weight participants. In overweight/obese, the independent correlates were waist circumference (odds ratio for 1 standard deviation increase = 3.78), alanine transaminase (2.11), BMI (2.00), male sex (1.74), triglycerides (1.44), systolic blood pressure (1.31), fasting insulin (1.23), and physical activity (0.76). In normal weight, the independent correlates included alanine transaminase (3.05), smoking (2.56), systolic blood pressure (1.54), and alcohol intake (1.41). In normal-weight participants, the associations with fatty liver were stronger for alcohol intake and smoking, and weaker for triglycerides, than in overweight/obese participants (P for interaction < 0.05). CONCLUSION Prevalence of fatty liver was 29% in overweight/obese and 5% in normal-weight adults. Differences in factors associated with fatty liver were seen between these two groups: alcohol intake and smoking were more strongly and triglycerides more weakly associated in normal-weight than in overweight/obese participants.
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Affiliation(s)
- Emmi Suomela
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku , Turku , Finland
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Bedogni G, Nobili V, Tiribelli C. Epidemiology of fatty liver: An update. World J Gastroenterol 2014; 20:9050-9054. [PMID: 25083078 PMCID: PMC4112887 DOI: 10.3748/wjg.v20.i27.9050] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 12/11/2013] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
We provide a concise review of the main epidemiological literature on fatty liver (FL) published between January 2011 and October 2013. The findings from the literature will be considered in light of the already available knowledge. We discuss the limitations inherent in the categorization of FL into non-alcoholic and alcoholic FL, the potential relevance of FL as an independent predictor of cardiometabolic disease, and recent research addressing the role of FL as an independent predictor of mortality. This review is organized as a series of answers to relevant questions about the epidemiology of FL.
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Pan JJ, Fallon MB. Gender and racial differences in nonalcoholic fatty liver disease. World J Hepatol 2014; 6:274-283. [PMID: 24868321 PMCID: PMC4033285 DOI: 10.4254/wjh.v6.i5.274] [Citation(s) in RCA: 232] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 12/14/2013] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of elevated liver enzymes. NAFLD represents a spectrum of liver injury ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may progress to advanced fibrosis and cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have higher overall mortality, cardiovascular mortality, and liver-related mortality compared with the general population. According to the population-based studies, NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and racial ethnic differences in NAFLD and NASH are likely attributed to interaction between environmental, behavioral, and genetic factors. Using genome-wide association studies, several genetic variants have been identified to be associated with NAFLD/NASH. However, these variants account for only a small amount of variation in hepatic steatosis among ethnic groups and may serve as modifiers of the natural history of NAFLD. Alternatively, these variants may not be the causative variants but simply markers representing a larger body of genetic variations. In this article, we provide a concise review of the gender and racial differences in the prevalence of NAFLD and NASH in adults. We also discuss the possible mechanisms for these disparities.
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Abstract
The liver plays a unique, central role in regulating lipid metabolism. In addition to influencing hepatic function and disease, changes in specific pathways of fatty acid (FA) metabolism have wide-ranging effects on the metabolism of other nutrients, extra-hepatic physiology, and the development of metabolic diseases. The high prevalence of nonalcoholic fatty liver disease (NAFLD) has led to increased efforts to characterize the underlying biology of hepatic energy metabolism and FA trafficking that leads to disease development. Recent advances have uncovered novel roles of metabolic pathways and specific enzymes in generating lipids important for cellular processes such as signal transduction and transcriptional activation. These studies have also advanced our understanding of key branch points involving FA partitioning between metabolic pathways and have identified new roles for lipid droplets in these events. This review covers recent advances in our understanding of FA trafficking and its regulation. An emphasis will be placed on branch points in these pathways and how alterations in FA trafficking contribute to NAFLD and related comorbidities.
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Manickam P, Sudhakar R. Dyslipidemia and non-alcoholic fatty liver disease. Dig Dis Sci 2013; 58:1435. [PMID: 23508978 DOI: 10.1007/s10620-013-2577-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Accepted: 01/15/2013] [Indexed: 12/15/2022]
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Younossi ZM, Otgonsuren M, Venkatesan C, Mishra A. In patients with non-alcoholic fatty liver disease, metabolically abnormal individuals are at a higher risk for mortality while metabolically normal individuals are not. Metabolism 2013; 62:352-60. [PMID: 22999011 DOI: 10.1016/j.metabol.2012.08.005] [Citation(s) in RCA: 144] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2012] [Revised: 08/01/2012] [Accepted: 08/13/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and is strongly associated with metabolic syndrome. The aim of this study is to compare the clinical profile and long-term outcome in NAFLD patients with or without metabolic syndrome. METHODS The initial cohort (N=6709) was identified from National Health and Nutrition Examination Survey-III (NHANES III, 1988-94) data. Laboratory profiles, body measurement examinations, and mortality data were linked to self-reported questionnaires of demographic and health risk information. NAFLD was defined as significant steatosis on hepatic ultrasound after exclusion of other chronic liver diseases (N=1448). NAFLD patients were classified according to presence or absence of metabolic syndrome. Mortality was determined through December 31, 2006. Cox models were used to estimate hazard ratios and 95% confidence intervals for all-cause, cardiovascular and liver-specific mortality differences between two sub-cohorts of NAFLD with and without metabolic syndrome. RESULTS NAFLD participants with metabolic syndrome were more likely to be Non-Hispanic white, older, and have higher aminotransferase levels. All-cause mortality (P<.001) and cardiovascular mortality (P<.001) were higher in NAFLD patients with metabolic syndrome. Furthermore, the presence of metabolic syndrome was independently associated with overall mortality, liver-specific mortality, and cardiovascular mortality. Age was an independent predictor of both all-cause and cardiovascular mortality. Elevated liver enzymes and obesity were two other independent predictors of liver-specific mortality. There were no differences in all-cause, liver-related, or cardiovascular mortality between groups of individuals without liver disease and individuals with NAFLD without metabolic syndrome (metabolically-normal). CONCLUSIONS Diagnosis of NAFLD with metabolic syndrome is an independent predictor of all-cause, liver-specific, and cardiovascular mortality. In contrast, mortality of metabolically-normal NAFLD patients is similar to the cohort without liver disease.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.
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